Esophageal Squamous Cell Carcinoma Abdominal Stage 0Phase 3EscapeNCT05737563
PD-1 Antibody Combined With mXELIRI Versus mXELIRI in the Second-line Setting for ESCC
A Phase 3 study testing PD-1 Inhibitors, Irinotecan and Capecitabine tablets in people with Esophageal Squamous Cell Carcinoma Abdominal Stage 0, run by Sun Yat-sen University at 1 site in China.
Trial summary
This trial is a prospective, multicenter, randomized controlled trial. The sample size was 380. Patients with advanced or metastatic esophageal squamous cell carcinoma will be randomized to receive PD1 antibody combined with mXELIRI or mXELIRI regimens in a 1:1 ratio. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma Abdominal Stage 0
- What is being tested?
- PD-1 Inhibitors, Irinotecan and Capecitabine tablets
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 1 siteChina
- Study dates
- 17 Feb 2023to 17 Feb 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily participate and sign the informed consent form
- Age≥ 18 years old, gender is not limited
- Estimated survival time≥ 3 months
- Physical status ECOG status score of 0 or 1
- metastatic esophageal squamous cell carcinoma, including patients with postoperative recurrence and metastasis that cannot be operated or are not suitable for radical radiotherapy, first-line chemotherapy combined with PD-1 antibody therapy is unsuccessful or intolerable (first-line chemotherapy does not use fluorouracils and irinotecan)
- If metastatic esophageal cancer has serious clinical symptoms due to lesions, palliative radiotherapy is required first, and radiotherapy is required to be completed for more than 4 weeks (radiotherapy lesions include but are not limited to primary lesions, bones, and lymph nodes)
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- Bone marrow hematopoietic function: hemoglobin ≥ 9.0g/dL, white blood cell ≥ 4.0×109/L, neutrophil ≥ 1.5×109/L, platelet ≥ 90×109/L
- Liver and kidney function: total bilirubin ≤ 1.5 × ULN, creatinine ≤ 1.0 × ULN, AST/ALT ≤ 2.5 ULN, ALP 5.0 ULN, creatinine clearance ≥ 60mL/min, subjects with liver metastases: AST/ALT ≤5.0 ULN
- Female subject must have taken reliable contraceptive measures of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last administration of the test drug. Male subject should agree to use appropriate contraceptive methods or to have been surgically sterilized during the trial and 8 weeks after the last administration of the test drug
- Those who have good compliance and can follow up according to the requirements of the plan.
Who cannot join
- previous useing of fluorouracil or irinotecan for metastatic disease;
- received radiotherapy within 4 weeks prior to enrollment;
- patients with symptomatic brain metastases;
- uncontrolled pleural effusion, pericardial effusion, or ascites that requires repeated drainage (once a month or more frequently); Multi-segment vertebral bone metastasis, easy to cause fracture, risk of paraplegia bone metastasis patients. Except for patients who are assessed by a specialist to be stable and do not need to be treated for the time being;
- Patients who are known to have complete endoscopic obstruction and require interventional treatment or surgery to relieve obstruction and who have undergone tracheal or esophageal stenting;
- Can not take oral medication;
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- BMI less than 17.5kg/m2, weight loss of >10% within about 2 months before the first administration of study treatment (need to consider a large number of pleural ascites changes) or other indicators show severe malnutrition;
- Those who are allergic to the drugs used in this program or their components;
- patients receiving chronic or multi-dose corticosteroid therapy (inhaled steroids or short-term oral cortisol as clinically indicated are allowed);
- History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-related vascular thrombosis, Wegener's granulomatous disease, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, etc. Patients who are hypothyroid but receiving a stable dose of thyroid hormone replacement therapy may be enrolled in this study; Patients with type 1 diabetes who are treated with a stable dose of insulin dosing regimen and whose blood glucose is controlled may be enrolled in this study;
- Patients with positive human immunodeficiency virus (HIV) test results
- Patients with active pulmonary tuberculosis (clinical diagnosis includes clinical history, physical examination and imaging findings, and TB examination according to local medical practice);
- received oral or intravenous antibiotics within 2 weeks prior to randomization; Patients receiving prophylactic antibiotic therapy (eg, to prevent urinary tract infection or to prevent exacerbation of chronic obstructive pulmonary disease) may be enrolled.
- Important cardiovascular diseases, such as heart disease (grade II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to randomization, unstable arrhythmia, unstable angina, cerebrovascular accident or transient ischemic attack; 50% of patients with known coronary artery disease, congestive heart failure that does not meet the above criteria, or left ventricular ejection fraction < must be treated with a stable regimen deemed best by the attending physician, and if necessary, a cardiologist;
- Chronic hepatitis B carriers with untreated chronic hepatitis B or HBV DNA > 1000 IU/mL at the time of screening. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA < 1000 IU/mL) can be enrolled;
- Had major surgery (other than diagnostic surgery) within 28 days prior to randomization, or was expected to undergo major surgery during the study period;
- Previous allogeneic bone marrow transplantation or solid organ transplantation;
- Patients with serious complications, such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, and active infection; Including but not limited to infection complications requiring hospitalization, bacteremia, severe pneumonia, etc.; history of idiopathic pulmonary fibrosis, organising pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, interstitial pneumonia, or evidence of active pneumonia on chest CT scan screening;
- Neurological or psychiatric abnormalities affecting cognitive ability;
- pregnant or lactating women;
- Those who have participated in other clinical studies in the past 30 days;
- Previous PD1 antibody therapy with grade 3 immune-related adverse reactions greater than or equal to 3
- Patients with other primary malignant tumors other than esophageal cancer (except cured skin basal cell carcinoma and cervical carcinoma in situ);
- Any other disease, metabolic disorder, abnormal result of physical examination or laboratory test that has reason to suspect may lead to contraindications to the use of the investigational drug, or affect the reliability of the results of the study, or put the patient at high risk of treatment complications.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, GD, 510060
Miao-Zhen Qiu, MD, PhD, +862087343351, qiumzh@sysucc.org.cn
Rui-Hua Xu
About this study
Official title: A Phase III, Randomized, Multicenter Study of PD-1 Antibody Combined With mXELIRI Versus mXELIRI in the Second-line Treatment of Metastatic Esophageal Squamous Cell Carcinoma
This trial is a prospective, multicenter, randomized controlled trial. The sample size was 380. Patients with advanced or metastatic esophageal squamous cell carcinoma will be randomized to receive PD1 antibody combined with mXELIRI or mXELIRI regimens in a 1:1 ratio. The stratification factors include PS status (0 vs 1), PFS of first-line treatment (PFS < 3 months versus PFS ≥3 months) . Six cycles of chemotherapy are planned every 3 weeks, for a total of 18 weeks, after which the investigator can decide whether to provide capecitabine with or without PD1 antibody maintenance therapy. Efficacy assessments were performed every 6 weeks before disease progression during treatment. Survival status was followed every 3 months after disease progression.
Read the detailed description
Esophageal cancer is the seventh most common cancer and the sixth most common cause of cancer related death worldwide. Globally, there were 604,000 new cases of esophageal cancer and 544,000 deaths in 2020. China is in the high incidence area of esophageal cancer, with 253,000 new cases of esophageal cancer and 194,000 deaths in 2016. Esophageal cancer has become a malignant disease that seriously endangers the health and social development.
Squamous cell carcinoma and adenocarcinoma are common pathological types of esophageal cancer. The main risk factors for esophageal squamous cell carcinoma are smoking and alcohol consumption. Esophageal squamous cell carcinoma is the most important pathological type of esophageal cancer in China, accounting for more than 90% of esophageal cancer.
The prognosis of esophageal cancer is very poor, most patients are in the middle and advanced stages at the time of diagnosis. The natural course of the disease is only 6-8 months, and the 5-year survival rate is less than 20%. In addition, 90% of patients undergoing surgery may have recurrent metastasis, and even those with very early staging (T1) still have the risk of relapse or metastasis within 5 years. Therefore, in recent years, scholars from various countries have continued to explore effective treatment methods in order to improve the quality of life and prolong the survival of esophageal cancer patients.
Palliative chemotherapy is the mainstay of treatment for advanced metastatic esophageal cancer including paclitaxel, platinum, fluorouracil, or irinotecan. Multiple phase III clinical studies have shown that PD-1 antibodies in addition to PF (fluorouracil plus cisplatin) or TP (paclitaxel plus cisplatin) regimens can improve the effective rate and prolong PFS and OS. Therefore, PD-1 antibody combined with chemotherapy has become the new standard first-line treatment for patients with advanced esophageal cancer.
Prior to the advent of PD-1 antibodies, the second-line regimen for advanced esophageal cancer was to select drugs that were not used in first-line chemotherapy, such as taxans or irinotecans. Keynote181, Attraction-03, and ESCORT studies have suggested that PD-1 antibody monotherapy is superior to standard chemotherapy in the second-line treatment of advanced esophageal cancer. In ESCORT studies, PD-1 antibodies and conventional chemotherapy (docetaxel or irinotecan) were 20.2 percent and 6.4 percent effective, median PFS at 1.9 months, and median OS at 8.3 months and 6.2 months, respectively. Based on the above research results, China's Food and Drug Administration has approved PD-1 antibody for the second-line treatment of advanced esophageal cancer.
Therefore, we intend to design a prospective, multicenter, randomized controlled clinical study based on the characteristics of esophageal cancer in China, explore the efficacy and safety of PD-1 antibody combined with mXELIRI compared with mXELIRI in the second-line treatment of metastatic esophageal squamous cell carcinoma. We will further analyze the significance of cross-line use of PD-1 antibody and analyze the possible benefit population.
- Being tested
- PD-1 Inhibitors, Irinotecan, Capecitabine tablets
- Keywords
- PD-1 inhibitor, Capecitabine, Irinotecan, Second-line, Esophageal Squamous Cell Carcinoma
- Medical subject headings
- Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 InhibitorsDrug
Teripulimab 240mg, injection or Carrelizumab 200mg, injection, every 3 weeks.
IrinotecanDrug
Irinotecan: 200mg/m2, injection (For patients who are confirmed to be homozygous for UGT1A1*6 or UGT1A1*28 or UGT1A1*6 and UGT1A1*28 at the same time, the starting dose of CPT-11 is 150 mg/m2).
Capecitabine tabletsDrug
Capecitabine: 1600 mg/m2/d, oral, 2 weeks on and 1 week off.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | PD-1 Antibody Combined With mXELIRI Receives: Drug: PD-1 Inhibitors; Drug: Irinotecan; Drug: Capecitabine tablets |
| Control | Active comparator | mXELIRI Receives: Drug: Irinotecan; Drug: Capecitabine tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
The time from registration to death due to any cause, or censored at date last known alive.
Measured: Up to 1 year
Secondary outcomes (3)
Progression free survival (PFS)
PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measured: Up to 1 year
Objective response rate (ORR)
Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Measured: Up to 6 months
Disease Control Rate (DCR)
Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start17 Feb 2023
- Primary completion17 Feb 2026 (estimated)
- Study completion17 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal Squamous Cell Carcinoma Abdominal Stage 0Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Junshi Bioscience Co., Ltd., Jiangsu HengRui Medicine Co., Ltd.
- Responsible party
- Principal investigator, Rui-hua Xu, MD, PhD, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737563
- Sponsor's protocol ID
- mXELIRI in ESCC
- Acronym
- Escape
- Status last verified
- Jan 2024
- First submitted
- 12 Feb 2023
- Last updated
- 23 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Multicenter Study of PD-1 Antibody Combined With mXELIRI Versus mXELIRI in the Second-line Treatment of Metastatic Esophageal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT05737563
- Acronym / sponsor ID
- Escape / mXELIRI in ESCC
- Keywords
- PD-1 inhibitor, Capecitabine, Irinotecan, Second-line, Esophageal Squamous Cell Carcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Shanghai Junshi Bioscience Co., Ltd., Jiangsu HengRui Medicine Co., Ltd.
- Study start
- 17 Feb 2023 (actual)
- Primary completion
- 17 Feb 2026 (estimated)
- Study completion
- 17 Feb 2026 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is a prospective, multicenter, randomized controlled trial. The sample size was 380. Patients with advanced or metastatic esophageal squamous cell carcinoma will be randomized to receive PD1 antibody combined with mXELIRI or mXELIRI regimens in a 1:1 ratio. The stratification factors include PS status (0 vs 1), PFS of first-line treatment (PFS < 3 months versus PFS ≥3 months) . Six cycles of chemotherapy are planned every 3 weeks, for a total of 18 weeks, after which the investigator can decide whether to provide capecitabine with or without PD1 antibody maintenance therapy. Efficacy assessments were performed every 6 weeks before disease progression during treatment. Survival status was followed every 3 months after disease progression.
Detailed description
Esophageal cancer is the seventh most common cancer and the sixth most common cause of cancer related death worldwide. Globally, there were 604,000 new cases of esophageal cancer and 544,000 deaths in 2020. China is in the high incidence area of esophageal cancer, with 253,000 new cases of esophageal cancer and 194,000 deaths in 2016. Esophageal cancer has become a malignant disease that seriously endangers the health and social development.
Squamous cell carcinoma and adenocarcinoma are common pathological types of esophageal cancer. The main risk factors for esophageal squamous cell carcinoma are smoking and alcohol consumption. Esophageal squamous cell carcinoma is the most important pathological type of esophageal cancer in China, accounting for more than 90% of esophageal cancer.
The prognosis of esophageal cancer is very poor, most patients are in the middle and advanced stages at the time of diagnosis. The natural course of the disease is only 6-8 months, and the 5-year survival rate is less than 20%. In addition, 90% of patients undergoing surgery may have recurrent metastasis, and even those with very early staging (T1) still have the risk of relapse or metastasis within 5 years. Therefore, in recent years, scholars from various countries have continued to explore effective treatment methods in order to improve the quality of life and prolong the survival of esophageal cancer patients.
Palliative chemotherapy is the mainstay of treatment for advanced metastatic esophageal cancer including paclitaxel, platinum, fluorouracil, or irinotecan. Multiple phase III clinical studies have shown that PD-1 antibodies in addition to PF (fluorouracil plus cisplatin) or TP (paclitaxel plus cisplatin) regimens can improve the effective rate and prolong PFS and OS. Therefore, PD-1 antibody combined with chemotherapy has become the new standard first-line treatment for patients with advanced esophageal cancer.
Prior to the advent of PD-1 antibodies, the second-line regimen for advanced esophageal cancer was to select drugs that were not used in first-line chemotherapy, such as taxans or irinotecans. Keynote181, Attraction-03, and ESCORT studies have suggested that PD-1 antibody monotherapy is superior to standard chemotherapy in the second-line treatment of advanced esophageal cancer. In ESCORT studies, PD-1 antibodies and conventional chemotherapy (docetaxel or irinotecan) were 20.2 percent and 6.4 percent effective, median PFS at 1.9 months, and median OS at 8.3 months and 6.2 months, respectively. Based on the above research results, China's Food and Drug Administration has approved PD-1 antibody for the second-line treatment of advanced esophageal cancer.
Therefore, we intend to design a prospective, multicenter, randomized controlled clinical study based on the characteristics of esophageal cancer in China, explore the efficacy and safety of PD-1 antibody combined with mXELIRI compared with mXELIRI in the second-line treatment of metastatic esophageal squamous cell carcinoma. We will further analyze the significance of cross-line use of PD-1 antibody and analyze the possible benefit population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: PD-1 Inhibitors, Drug: Irinotecan, Drug: Capecitabine tabletsPD-1 Antibody Combined With mXELIRI |
| Control | Active comparator | Drug: Irinotecan, Drug: Capecitabine tabletsmXELIRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Voluntarily participate and sign the informed consent form
- Age≥ 18 years old, gender is not limited
- Estimated survival time≥ 3 months
- Physical status ECOG status score of 0 or 1
- metastatic esophageal squamous cell carcinoma, including patients with postoperative recurrence and metastasis that cannot be operated or are not suitable for radical radiotherapy, first-line chemotherapy combined with PD-1 antibody therapy is unsuccessful or intolerable (first-line chemotherapy does not use fluorouracils and irinotecan)
Key exclusion criteria (24 listed)
- previous useing of fluorouracil or irinotecan for metastatic disease;
- received radiotherapy within 4 weeks prior to enrollment;
- patients with symptomatic brain metastases;
- uncontrolled pleural effusion, pericardial effusion, or ascites that requires repeated drainage (once a month or more frequently); Multi-segment vertebral bone metastasis, easy to cause fracture, risk of paraplegia bone metastasis patients. Except for patients who are assessed by a specialist to be stable and do not need to be treated for the time being;
- Patients who are known to have complete endoscopic obstruction and require interventional treatment or surgery to relieve obstruction and who have undergone tracheal or esophageal stenting;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1 InhibitorsTeripulimab 240mg, injection or Carrelizumab 200mg, injection, every 3 weeks. | Drug | Experimental |
| IrinotecanIrinotecan: 200mg/m2, injection (For patients who are confirmed to be homozygous for UGT1A1*6 or UGT1A1*28 or UGT1A1*6 and UGT1A1*28 at the same time, the starting dose of CPT-11 is 150 mg/m2). | Drug | Control, Experimental |
| Capecitabine tabletsCapecitabine: 1600 mg/m2/d, oral, 2 weeks on and 1 week off. | Drug | Control, Experimental |
Primary outcome
Overall survival (OS)
Time frame: Up to 1 year
The time from registration to death due to any cause, or censored at date last known alive.
3 secondary outcomes
Progression free survival (PFS)
Time frame: Up to 1 year
Objective response rate (ORR)
Time frame: Up to 6 months
Disease Control Rate (DCR)
Time frame: Up to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PD-1 Inhibitors, Irinotecan and Capecitabine tablets in people with Esophageal Squamous Cell Carcinoma Abdominal Stage 0, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.